A detailed investigation of the structure of tRNA in solution will be carried out using NMR as the principal experimental tool. This work is based on the discovery that hydrogen bonded protons of Watson-Crick base pairs in tRNA can be observed in aqueous solution quite far (5 - 10 ppm) downfield from the water peak. There is a 1 to 1 correspondence between resonances in the low field spectrum and base pairs in the molecule, and therefore the NMR permits us to examine in great deal the secondary and tertiary structure of tRNA molecules, and changes in conformation which occur in response to chemical modification, pH, temperature and presence or absence of mono- and divalent-cations. The major goal of this work will be to determine the complete secondary and tertiary structure of yeast tRNA Phe, and other tRNA molecules in solution. A number of different approaches to this problem have been implemented and are beginning to yield the necessary information.